New University of Virginia School of Medicine research is shedding light on how federal funding helped scientists understand the COVID-19 virus, develop new treatments and deploy lifesaving vaccines in record time.
The UVA Health researchers used advanced “machine learning” — a form of artificial intelligence — to analyze the thousands of scientific publications that resulted from the National Institutes of Health’s deployment of more than $4 billion to combat the pandemic. This analysis allowed the researchers to categorize the types of research the money supported and determine how and where the funding was used to launch clinical trials of treatments and vaccines.
“The COVID-19 pandemic presented an unprecedented public-health challenge. The scientific community needed to rapidly act to come up with solutions to not only combat the virus but understand how we can prevent something like this from happening again,” said Taison D. Bell, MD, of UVA Health’s Division of Pulmonary and Critical Care Medicine and Division of Infectious Diseases and International Health. “The NIH is the largest public funder of biomedical research, so we believe it was vital to study how $4 billion of NIH funding was allocated and used during the pandemic.”
Acting Fast Amid the COVID-19 Pandemic
The UVA researchers used advanced tools they have developed over the last eight years to analyze more than 14,600 scientific publications funded by more than 2,400 federal grants awarded between January 2020 and December 2021. Most of the publications appeared in peer-reviewed scientific journals, but some appeared on what are known as “preprint servers.” Preprint servers allow scientists to share their discoveries with their colleagues quickly, but, unlike peer-reviewed journals, the findings are not vetted by other scientists prior to publication.
UVA’s machine-learning model determined that the top three research topics investigated by COVID-related publications were clinical trials and outcomes research (8.5% of papers), coronavirus-related heart and lung damage (7.3%), and COVID-19 transmission/epidemiology (7.2%). But scientists used the money to investigate not only science directly related to the virus itself, but also related areas such as vaccine hesitancy, effective vaccine distribution, health disparities and general virology (the study of viruses), the UVA researchers found.
Five states received approximately half of the $4 billion in emergency COVID-19 funding, the analysis reveals: North Carolina, Washington, New York, California and Massachusetts. Of the more than 1,800 clinical trial sites testing treatments and vaccines, most, unsurprisingly, were in major urban areas where COVID had stricken many people, the researchers found. (Clinical trials, in general, tend to take place in more urban areas where it is easier to recruit volunteers.)
The Importance of Preprints

In a new scientific paper outlining their findings, the UVA researchers note the rise of preprint servers during the pandemic: “During the pandemic, this fast dissemination of basic science in preprint servers may have supported hypothesis generation and preliminary validation for groups to augment their research,” they wrote. “The higher proportion of cell/molecular studies in preprint servers indicates that researchers may have wanted to expedite access to highly valuable data early in the pandemic to foster further scientific inquiry and collaboration at the basic science level in areas such as SARS CoV-2 transmission and vaccine development. There might also be an element of authors initially submitting to preprints if they believed their work could be subject to a long peer-review process because, perhaps, of a shortage of reviewers in their target journals during the pandemic.”
The UVA researchers are urging additional research to do a deeper dive into what they found and to look at, for example, the results of other COVID funding sources, such as private philanthropy and the Department of Defense. By understanding how COVID research funding was used and the benefits it had, the country will be better prepared to respond to the next pandemic, they say.
“This work is the first to shed light on how billions of federal money was used to study and combat the COVID-19 pandemic,” said researcher Ani Chandrabhatla. “The framework and software we developed to study NIH funding helped us understand where and how funding was deployed and, even more, what topics researchers were studying with that funding.”
Findings Published
The researchers have published their findings in a pair of papers in the scientific journal Open Forum Infectious Diseases. The research team included Adishesh K. Narahari, Anirudha S. Chandrabhatla, Taylor M. Horgan, D. Chris Gist, Mark A. Lantieri, Paranjay D. Patel, Jeffrey M. Sturek, Claire L. Davis, Patrick E. H. Jackson and Taison D. Bell.

The American Cancer Society hopes to enroll 100,000 women and follow them for three decades to discover what’s causing higher case and death rates.The American Cancer Society has begun an ambitious, far-reaching study focusing on a population that has long been overlooked, despite high rates of cancer and cancer-related deaths: Black women.The initiative, called VOICES of Black Women, is believed to be the first long-term population study of its size to zero in specifically on the factors driving cancer prevalence and deaths among Black women.Researchers plan to enroll 100,000 Black women without cancer, ages 25 to 55, in Washington, D.C., and 20 states where most Black American women reside. The subjects will be surveyed twice a year about their behaviors, environmental exposures and life experiences, and followed for 30 years; any cancers they may develop will be tracked.Similar studies by the American Cancer Society in the past yielded critical lessons about what causes cancer — for example, identifying cigarette smoking as a cause of lung cancer and linking red- and processed-meat consumption to increased risk of colon cancer.While some earlier studies have included large numbers of Black women, the research wasn’t able to “hone in on the specific drivers of cancer in that population,” said Dr. Alpa Patel, senior vice president of population science at the society and co-principal investigator of the VOICES study, along with Dr. Lauren McCullough.“In general population studies, you tend to ask questions that are going to be applicable to the majority of the population,” she said. “So going deeply into the lived experiences of discrimination, bias, systematic issues, environmental influences and cultural aspects of health-related behaviors, and how the narratives around them are shaped in different populations — those types of unique aspects of understanding what contributes to cancer in a population weren’t being asked about.”We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Biomedical engineers at Duke University have developed a silk-based, ultrathin membrane that can be used in organ-on-a-chip models to better mimic the natural environment of cells and tissues within the body. When used in a kidney organ-on-a-chip platform, the membrane helped tissues grow to recreate the functionality of both healthy and diseased kidneys.
By allowing the cells to grow closer together, this new membrane helps researchers to better control the growth and function of the key cells and tissues of any organ, enabling them to more accurately model a wide range of diseases and test therapeutics.
The research appears June 4 in the journal Science Advances.
Often no larger than a USB flash drive, organ-on-a-chip (OOC) systems have revolutionized how researchers study the underlying biology of the human body, whether it’s creating dynamic models of tissue structures, studying organ functions or modeling diseases. These platforms are designed to stimulate cell growth and differentiation in a way that best mimics the organ of interest. Researchers can even populate these tools with human stem cells to generate patient-specific organ models for pre-clinical studies.
But as the technology has evolved, problems in the chip’s design have also emerged — most notably with the materials used to create the membranes that form the support structure for the specialized cells to grow on. These membranes are typically composed of polymers that don’t degrade, creating a permanent barrier between cells and tissues. While the extracellular membranes in human organs are often less than one micron thick, these polymer membranes are anywhere from 30 to 50 microns, hindering communication between cells and limiting cell growth.
“We want to handle the tissues in these chips just like a pathologist would handle biopsy samples or even living tissues from a patient, but this wasn’t possible with the standard polymer membranes because the extra thickness prevented the cells from forming structures that more closely resemble tissues in the human body,” said Samira Musah, an assistant professor of biomedical engineering and medicine at Duke. “We thought, ‘Wouldn’t it be nice if we could get a protein-based material that mimics the structure of these natural membranes and is thin enough for us to slice and study?'”
This question led Musah and George (Xingrui) Mou, a PhD student in Musah’s lab and first author on the paper, to silk fibroin, a protein created by silkworms that can be electronically spun into a membrane. When examined under a microscope, silk fibroin looks like spaghetti or a Jackson Pollock painting. Made out of long, intertwining fibers, the porous material better mimics the structure of the extracellular matrix found in human organs, and it has previously been used to create scaffolds for purposes like wound healing.

“The silk fibroin allowed us to bring the membrane thickness down from 50 microns to five or fewer, which gets us an order of magnitude closer to what you’d see in a living organism,” explained Mao.
To test this new membrane, Musah and Mao applied the material to their kidney chip models. Made out of a clear plastic and roughly the size of a quarter, this OOC platform is meant to resemble a cross section of a human kidney — specifically the glomerular capillary wall, a key structure in the organ made from clusters of blood vessels that is responsible for filtering blood.
Once the membrane was in place, the team added human induced pluripotent stem cell derivatives into the chip. They observed that these cells were able to send signals across the ultrathin membrane, which helped the cells differentiate into glomerular cells, podocytes and vascular endothelial cells. The platform also triggered the development of endothelial fenestrations in the growing tissue, which are holes that allow for the passage of fluid between the cellular layers.
By the end of the test, these different kidney cell types had assembled into a glomerular capillary wall and could efficiently filter molecules by size.
“The new microfluidic chip system’s ability to simulate in vivo-like tissue-tissue interfaces and induce the formation of specialized cells, such as fenestrated endothelium and mature glomerular podocytes from stem cells, holds significant potential for advancing our understanding of human organ development, disease progression, and therapeutic development,” said Musah.
As they continue to optimize their model, Musah and colleagues are hoping to use this technology to better understand the mechanisms behind kidney disease. Despite affecting more than 15 percent of American adults, researchers lack effective models for the disease. Patients are also often not diagnosed until the kidneys have been substantially damaged, and they are often required to undergo dialysis or receive a kidney transplant.
“Using this platform to develop kidney disease models could help us discover new biomarkers of the disease,” said Mao. “This could also be used to help us screen for drug candidates for several kidney disease models. The possibilities are very exciting.”
“This technology has implications for all organ-on-a-chip models,” said Musah. “Our tissues are made up of membranes and interfaces, so you can imagine using this membrane to improve models of other organs, like the brain, liver, and lungs, or other disease states. That’s where the power of our platform really lies.”
This work was supported by a Whitehead Scholarship in Biomedical Research, Chair’s Research Award from the Department of Medicine at Duke University, MEDx Pilot Grant on Biomechanics in Injury or Injury Repair, Burroughs Wellcome Fund PDEP Career Transition Ad Hoc Award, Duke Incubation Fund from the Duke Innovation & Entrepreneurship Initiative, Genetech Research Award, a George M. O’Brien Kidney Center Pilot Grant (P30 DK081943), an NIH Director’s New Innovator Grant (DP2DK138544).

Researchers at The University of Texas at El Paso are developing a new therapeutic approach that uses nanoparticles for the treatment of skin and lung fibrosis, conditions that can result in severe damage to the body’s tissues.
Md Nurunnabi, Ph.D., is an associate professor in UTEP’s School of Pharmacy and the lead researcher on two studies published this June in the medical Journal of Controlled Release; one study focuses on skin fibrosis and the other on lung fibrosis.
“We are closer than ever to developing a safe, effective and reliable approach to treating fibrosis,” Nurunnabi said.
Fibrosis is a condition in which the tissues in an organ — such as the skin, lungs, liver or kidneys — become thicker and stiffer, according to Nurunnabi. This can have multiple damaging effects, such as the lungs not being able to hold enough oxygen or blood vessels becoming narrower, leading to high blood pressure.
“I studied fibrosis during my postdoctoral training but became interested in focusing on it in my lab during the COVID-19 pandemic,” Nurunnabi said. “I observed that many people were passing away not because of COVID itself, but because of the inflammation and fibrosis caused by the viral infection in the lungs. Our lab focuses on developing nanotechnology that can target specific cells.”
Fibrosis can occur as a side effect of chemotherapy or the result of a viral infection or autoimmune disease, a condition in which the body’s immune system attacks its own cells. For example, with an autoimmune condition, the body kills cells called fibroblasts that help form connective tissue. The body then produces more collagen than it needs, which leads to fibrosis.
Nurunnabi’s team focused on designing a nanoparticle that could target the cells that are responsible for fibrosis development and progression without disturbing the “good” cells necessary for the body’s healthy functioning. Rather than killing the “bad” cells, the team was successful in modifying them so that they no longer produced excess collagen, in effect rehabilitating the cells. The studies were conducted in the test tube and in mice.
“Dr. Nurunnabi’s research into skin and lung fibrosis sheds light on the devastating impact of these conditions, whether acute or chronic,” said José Rivera, Pharm.D, founding dean of the School of Pharmacy. “His findings offer hope for improved treatments that could significantly increase life expectancy and enhance the quality of life for affected individuals.”
Nurunnabi’s lab is funded through a collaborative program between UTEP, the National Institutes of Health and Baylor College of Medicine, as well as a pilot grant from the National Scleroderma Foundation to conduct research related to treatment of fibrosis.

In a new study funded by the U.S. Centers for Disease Control and Prevention, researchers from Yale and 11 other institutions found “no association between COVID-19 vaccination and stillbirth.”
In a case-control study led by Yale School of Medicine’s Dr. Anna Denoble, researchers compared 276 stillbirths with 822 live births during a one-year period from February 2021 to February 2022. Their results, published June 6 in the journal Obstetrics & Gynecology, found no linkage between pregnant individuals receiving a COVID-19 vaccine and stillbirth outcomes.
“Stillbirth is a heartbreaking experience for parents,” said Denoble, assistant professor of obstetrics, gynecology and reproductive sciences and first author of the study. “Expecting parents don’t want to do anything that might harm their pregnancy. We wanted to provide reassurance surrounding COVID-19 vaccine in pregnancy by carefully exploring whether there was any association with stillbirth. We found no association.”
Yale’s Dr. Sangini Sheth, an associate professor of obstetrics, gynecology and reproductive sciences was also part of the research team.
While vaccine hesitancy remains a public health challenge, the researchers noted, the results show that “vaccination remains the most effective tool for preventing hospitalizations and morbidity due to COVID-19 and is recommended in pregnancy by the CDC and the American College of Obstetricians and Gynecologists.”
For the study, the researchers analyzed hundreds of records from the CDC’s Vaccine Safety Datalink [VSD], comparing receipt of the COVID-19 vaccine during pregnancy between those who had stillbirths [defined as fetal death at or beyond 20 weeks of pregnancy] and those who had live births. Each confirmed stillbirth was compared with up to three live births that had similar variables, including maternal age, pregnancy start date, health care site, and exposure to at least one COVID-19 vaccination during pregnancy. There was no significant difference in COVID-19 vaccination between the two groups.
According to their findings, 38.4% of patients experiencing stillbirth received a COVID-19 vaccine in pregnancy compared with 39.3% of those with live births.
The researchers also found “no association … detected by vaccine manufacturer or number of doses received during pregnancy.” Denoble says this is all in line with additional research recently published by the same research team that also showed no difference in other pregnancy outcomes between those who were vaccinated and those who were not.
Denoble and co-authors say this research “has several strengths and advantages over previous studies” of the same topic. They point out that stillbirth cases were clinically reviewed by obstetrician investigators, “reducing misclassifications.” Also, a larger number of stillbirth cases were included and the use of the VSD provided comprehensive COVID-19 vaccination data, “often not possible in other U.S. studies.”
“The results of this robust case-control study can be used to reassure both pregnant patients and health care professionals that COVID-19 vaccination in pregnancy is not associated with an increased risk of pregnancy loss,” said Denoble.

His marriage fell apart as his addiction to crack cocaine deepened. The Times would like to speak with families shaken by a loved one’s drug addiction.Hunter Biden, the president’s son, is being tried in federal court for falsely claiming on a gun purchase application that he did not use illicit drugs. Testimony from his ex-wife and former girlfriends describe his drug-fueled temper; his search for his dealer on the streets; his large cash withdrawals from the bank.Hallie Biden, the widow of his brother Beau who dated him during the fall of 2018 when the gun purchase took place, spoke of his erratic behavior, his possession of rocks of crack cocaine “the size of Ping-Pong balls, or bigger, maybe” and how she frantically urged him to go to rehab. She, like Mr. Biden, is in recovery.I write about addiction for The New York Times and have spoken with countless families who have shared wrenching experiences. I’m working on an article about how the Bidens’ addiction saga is reverberating for families who are also grappling with America’s deadly addiction crisis.To better understand evolving public views toward addiction, I would like to hear your stories. I’ll read each response and reach out if I’d like to learn more. I won’t publish any part of your response without following up and verifying your information. And I won’t share your contact information outside the Times newsroom or use it for any reason other than to get in touch with you.

Preliminary clinical data for glioblastoma multiforme patients enrolled in a Phase 1 clinical trial at the University of Alabama at Birmingham demonstrated that 92 percent of evaluable patients treated with INB-200 exceeded a median progression-free survival of seven months with concomitant temozolomide chemotherapy. The median follow-up was 11.7 months.
This survival data along with radiographic improvements are indicative of positive treatment effects, which highlights the potential of IN8bio’s genetically modified, chemotherapy-resistant gamma-delta T cells as a potential first-in-class therapy for patients with newly diagnosed glioblastoma. Glioblastoma multiforme is the most aggressive type of cancer originating in the brain.
The clinical trial was led by Burt Nabors, M.D., in collaboration with IN8bio. Nabors is a professor of neurology at UAB, division director of Neuro-Oncology and a senior scientist in the O’Neal Comprehensive Cancer Center at UAB. Gamma-delta T cells are a specialized population of T cells that possess unique properties, including the ability to differentiate between healthy and diseased tissue.
IN8bio is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of gamma-delta T cell product candidates for solid and liquid tumors. Larry Lamb, Ph.D., former professor in the UAB Marnix E. Heersink School of Medicine Department of Medicine, and the scientific co-founder and current chief scientific officer at IN8bio Inc., helped develop the technology. INB-200 is the first genetically modified gamma-delta T cell therapy to enter clinical trials. The UAB intellectual property is licensed through the Bill L. Harbert Institute for Innovation and Entrepreneurship.
The current standard of care for newly diagnosed glioma patients consists of primary resection and six weeks of daily chemoradiation therapy, followed by six cycles of monthly maintenance temozolimide therapy. This Stupp regimen achieves a median progression-free survival of seven months and an overall survival of approximately 14 to 16 months.
The Phase 1 study assessed the safety and preliminary efficacy of adding DeltEx DRI gamma-delta T cells to maintenance therapy with temozolomide. The trial assessed the administration of 10 million cells per dose across three different dosing regimens increasing from a single dose delivered on Cycle 1, Day 1 during maintenance in Cohort 1, to three doses delivered on Day 1 of Cycles 1-3 in Cohort 2, to six doses delivered on Day 1 of Cycles 1-6 in Cohort 3. Thirteen patients have been enrolled and treated with INB-200, including three patients in Cohort 1 (one dose), four patients in Cohort 2 (three doses) and six patients in Cohort 3 (six doses). All of the patients in the Phase 1 study who received all of their protocol-defined treatments with INB-200 exceeded the median progression-free survival of seven months, including one patient in Cohort 2 who remains alive and progression-free after nearly three years.
“For far too long, there has been little advancement for patients with glioblastoma multiforme to improve their treatment outcomes,” Nabors said. “The addition of multiple intracranial injections of IN8bio’s DeltEX DRI gamma-delta T cells shows the potential for extending progression-free survival in this patient population, when administered in combination with the current standard of care used to treat newly diagnosed glioblastoma patients.”
No treatment-related serious adverse events have been reported in any cohort.

“The safety profile of gamma-delta T cells continues to be strong across all three dose cohorts with no cell therapy-related toxicities such as immune effector cell-associated neurotoxicity syndrome or cytokine release syndrome reported in patients receiving up to the maximum dose of six infusions of the therapy,” said Trishna Goswami, M.D., chief medical officer for IN8bio. “We are now dosing newly diagnosed patients in Arm A of a Phase 2 study with INB-400, evaluating up to six infusions of our autologous gamma-delta T cells in combination with the Stupp protocol.”
Radiographic evaluation pre- and post-treatment included resolution of midline shift in one patient with evidence of changes in enhancement attributed to treatment effect in multiple patients. One subject was found to have a 36 percent decrease in a lesion attributed to positive treatment effect. “As these encouraging results from our ongoing INB-200 Phase 1 study continue to mature, we look forward to reporting additional results from a long-term follow-up of Cohort 3 at future medical meetings,” said William Ho, CEO and co-founder of IN8bio.
These preliminary clinical data were presented at a poster session of the 2024 American Society of Clinical Oncology, or ASCO, Annual Meeting in Chicago. Mina Lobbous, M.D., assistant professor of neurology at Cleveland Clinic (after completing his Neuro-Oncology fellowship at UAB) was the poster presenter.

The role that Epstein-Barr Virus (EBV) plays in the development of multiple sclerosis (MS) may be caused a higher level of cross-reactivity, where the body’s immune system binds to the wrong target, than previously thought.
In a new study published in PLOS Pathogens, researchers looked at blood samples from people with multiple sclerosis, as well as healthy people infected with EBV and people recovering from glandular fever caused by recent EBV infection. The study investigated how the immune system deals with EBV infection as part of worldwide efforts to understand how this common virus can lead to the development of multiple sclerosis, following 20-years of mounting evidence showing a link between the two.
While previous studies have shown that antibody responses to one EBV protein — EBNA1 — also recognise a small number of proteins of the central nervous system, this study found that T-cells, another important part of the immune system, that target viral proteins can also recognise brain proteins.
A second important finding was that these cross-reactive T-cells can be found in people with MS but also in those without the disease. This suggests that differences in how these immune cells function may explain why some people get MS after EBV infection.
Dr Graham Taylor, associate professor at the University of Birmingham and one of the corresponding authors of the study said:
“The discovery of the link between Epstein-Barr Virus and Multiple Sclerosis has huge implications for our understanding of autoimmune disease, but we are still beginning to reveal the mechanisms that are involved. Our latest study shows that following Epstein-Barr virus infection there is a great deal more immune system misdirection, or cross-reactivity, than previously thought.”
“Our study has two main implications. First, the findings give greater weight to the idea that the link between EBV and multiple sclerosis is not due to uncontrolled virus infection in the body. Second, we have shown that the human immune system cross-recognises a much broader array of EBV and central nervous system proteins than previously thought, and that different patterns of cross-reactivity exist.

“Knowing this will help identify which proteins are important in MS and may provide targets for future personalised therapies.”
T Cells are involved
During testing of blood, the team also found evidence that cross-reactive T cells that target Epstein-Barr virus and central nervous system proteins are also present in many healthy individuals.
Dr Olivia Thomas from the Karolinska Institute in Sweden and joint corresponding author of the paper said:
“Our detection of cross-reactive T-cells in healthy individuals suggests that it may be the ability of these cells to access the brain that is important in MS.
“Although our work shows the relationship between EBV and MS is now more complex than ever, it is important to know how far this cross-reactivity extends to fully understand the link between them.”

The small protein ubiquitin is involved in almost every cellular process in our body: it orchestrates the stability and function of the vast majority of proteins. When it binds to other proteins, they are often released for degradation. However, this labelling can also be reversed by special enzymes. The enzyme USP28, for example, is known to stabilise proteins that are important for cell growth and division — these can also play an important role in cancer growth.
In order to reduce the stability of these proteins and thus inhibit cancer growth, inhibitors of USP28 have been developed. These inhibitors, which form the basis of many anti-cancer drugs currently in development, disrupt cell division by blocking the USP28 enzyme. The problem is that they often act not only against USP28 but also against USP25, a closely related enzyme that separates ubiquitin from other proteins and is considered a key protein of the immune system. Further development of USP28 inhibitors into therapeutics that can be used in the clinic is therefore very difficult because of the foreseeable side effects — ranging from gastrointestinal problems to nerve damage and even autoimmune diseases.
Risk of Confusion Between the Two Enzymes
Researchers at the University of Würzburg (JMU) have now discovered why inhibitors not only target USP28, but also USP25: “Apparently, there is a high risk of confusion between USP28 and USP25,” explains Caroline Kisker, Chair of Structural Biology at the Rudolf Virchow Centre in Würzburg and Vice President for Research and Young Scientists. “We have been able to show that the two enzymes are very similar or even identical in many areas, including precisely where the inhibitors act.”
As part of her research, the biochemist’s team used X-ray crystallography to analyse the structure of USP28 in combination with the three inhibitors “AZ1,” “Vismodegib” and “FT206” — and thus determine the spatial binding site. Further biochemical experiments on USP25 showed that the sites where the inhibitors bind to USP28 and USP25 are identical. “The inhibitors are therefore unable to distinguish where they bind,” says Kisker. “This explains the non-specific effect.”
Discovery Paves the Way for the Development of Precise Inhibitors
The new scientific findings provide an important basis for the search for more specific drugs with fewer side effects. Their development is the next major goal of the Würzburg researchers. “Our structural biology data allows us to modify existing inhibitors so that they only work against either USP25 or USP28,” says Kisker. “We also want to look for inhibitors that bind to less similar enzyme sites. This will give these molecules greater targeting precision.”
The research was funded by the German Research Foundation (DFG).
The Rudolf-Virchow-Centre in Würzburg
The Rudolf Virchow Centre (RVZ) for Integrative and Translational Imaging is an interdisciplinary research centre that focuses on the visualisation of elementary life processes — from the sub-nano to the macro scale. As a central institution of the University of Würzburg, the centre is currently home to 13 translational research groups and around 100 researchers investigating the molecular causes of health and disease.

National University of Singapore (NUS) chemists have developed a strategy using disulfide-containing small molecules to facilitate the reversible control and delivery of ribonucleic acid (RNA).
RNA-based therapeutics have emerged as one of the most sought-after therapeutic modalities in recent years. However, RNA delivery remains a major challenge in the field. Lipid nanoparticles, despite being widely used for RNA delivery including the delivery of Covid-19 mRNA vaccines, face several limitations such as their effectiveness and safety. Alternative methods that can potentially overcome these limitations are highly desirable.
A research team led by Assistant Professor ZHU Ru-Yi from the NUS Department of Chemistry have developed a method that takes advantage of a chemical process called post-synthetic RNA acylation chemistry, and combined it with dynamic disulfide exchange reaction for RNA delivery and reversible control. This method provides a way to mask the RNA molecule, and researchers can potentially regulate its activity and delivery until it reaches its target site within the cell.
The research findings were published in the journal Angewandte Chemie International Edition on 13 March 2024.
The researchers found that by adding special chemical markers comprising disulfide-containing groups to the RNA, these groups can block RNA’s catalytic activity and folding, temporarily hiding the instructions. Then, when needed, they can activate the RNA by removing these markers, allowing cells to read and act upon the instructions again. This strategy allows the RNA to enter cells quickly, distribute effectively, and become active in the cell’s cytosol without getting trapped in lysosomes. The researchers believe that their methodology will be accessible to laboratories engaged in RNA biology and holds promise as a versatile platform for RNA-based applications.
Asst Prof Zhu said, “Our studies showcase the first example of RNA delivery into cells using only small molecules.”
“The simplicity of our method for modifying RNA and the unique delivery mechanism will undoubtedly attract more researchers to adopt and improve the method. We believe that our work will facilitate numerous applications in the field of RNA biology and biomedicines,” added Asst Prof Zhu.
Looking ahead, the research team is actively designing new strategies to modify RNA and improve RNA-based therapeutics.